Ondansetron Tablets
DEFINITION
Ondansetron Tablets contain Ondansetron Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ondansetron (C18H19N3O).
IDENTIFICATION
•  A. Infrared Absorption 197K
Sample:  Transfer a portion of the powder from finely powdered Tablets, equivalent to 100 mg of ondansetron hydrochloride, to a suitable conical flask. Add 50 mL of alcohol, and swirl. Pass the liquid through a PTFE filter of 0.45-µm pore size into a 50-mL beaker. Evaporate the solvent on a rotary evaporator. Dry the precipitate in an air oven for 1 h at 105. Prepare a suitable dispersion of the residue in potassium bromide, and record the spectra of the Sample and the standard specimen in the spectral range 3800–650 cm1. [Note—It is recommended that a solution of USP Ondansetron Hydrochloride RS in alcohol be prepared at a concentration of 2 mg/mL before the evaporation, followed by the drying steps. ]
Acceptance criteria:  The Sample shows strong bands at 1621, 1481, 1281, and 758 cm1, similar to the potassium bromide dispersion of USP Ondansetron Hydrochloride RS.
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
Buffer:  2.7 g/L of monobasic potassium phosphate. Adjust with 1 N sodium hydroxide to a pH of 5.4.
Mobile phase:  Acetonitrile and Buffer (1:4)
Diluent:  Acetonitrile and Buffer (1:1)
Standard solution:  0.05 mg/mL of ondansetron (free base) in Diluent from USP Ondansetron Hydrochloride RS
Sample stock solution:  Weigh and finely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 50 mg of ondansetron, based on the label claim, to a 100-mL volumetric flask. Add 70 mL of Diluent, and sonicate for about 20 min. Dilute with Diluent to volume. Centrifuge a portion of the solution.
Sample solution:  Quantitatively dilute the supernatant with Diluent to obtain a solution having a nominal concentration of 0.05 mg/mL of ondansetron, based on the label claim. Pass through a suitable nylon filter of 0.45-µm pore size, and use the filtrate.
Chromatographic system 
Mode:  LC
Detector:  UV 216 nm
Column:  4.6-mm × 25-cm; 5-µm packing L10
Flow rate:  1.5 mL/min
Injection size:  10 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of the label claim of ondansetron (C18H19N3O) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of ondansetron (free base) in the Standard solution (mg/mL)
CU== nominal concentration of ondansetron in the Sample solution (mg/mL)
Acceptance criteria:  90.0%–110.0%
PERFORMANCE TESTS
Change to read:
•  Dissolution 711
Test 1 
Medium:  Water; 500 mL, deaerated
Apparatus 2:  50 rpm
Time:  15 min
Standard solution:  USP Ondansetron Hydrochloride RS in Medium in a concentration similar to the one expected in the Sample solution
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute, if necessary, with Medium.
Instrumental conditions 
Mode:  UV
Analytical wavelength:  310 nm
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== label claim (mg/Tablet)
Mr1== molecular weight of ondansetron, 293.36
Mr2== molecular weight of ondansetron hydrochloride (anhydrous), 329.83(RB 1-Jul-2011)
V== volume of Medium, 500 mL
Tolerances:  NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 2:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis:  Proceed as directed for Test 1.
Time:  30 min
Tolerances:  NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 3:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:  0.01 N hydrochloric acid; 500 mL, deaerated
Apparatus 2:  50 rpm
Time:  30 min
Standard solution:  Known concentration of USP Ondansetron Hydrochloride RS in Medium, close to the expected concentration of the Sample solution
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and dilute, if necessary, with Medium.
Instrumental conditions 
Mode:  UV
Analytical wavelength:  248 nm
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== label claim (mg/Tablet)
Mr1== molecular weight of ondansetron, 293.36
Mr2== molecular weight of ondansetron hydrochloride (anhydrous), 329.83(RB 1-Jul-2011)
V== volume of Medium, 500 mL
Tolerances:  NLT 80% (Q) of the labeled amount of C18H19N3O is dissolved.
Test 4:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:  0.1 N hydrochloric acid; 500 mL
Apparatus 2:  50 rpm
Time:  30 min
Standard stock solution:  450 µg/mL of USP Ondansetron Hydrochloride RS in Medium
Standard solution:  Dilute the Standard stock solution quantitatively and stepwise, if necessary, with Medium to obtain a final concentration of about (L/500) mg/mL, where L is the Tablet label claim, in mg.
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Instrumental conditions 
Mode:  UV
Analytical wavelength:  249 nm
Cell path:   1 cm for Tablets labeled to contain 4 or 8 mg; 0.2 cm for Tablets labeled to contain 16 or 24 mg
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== label claim (mg/Tablet)
Mr1== molecular weight of ondansetron, 293.36
Mr2== molecular weight of ondansetron hydrochloride (anhydrous), 329.83(RB 1-Jul-2011)
V== volume of Medium, 500 mL
Tolerances:  NLT 80% (Q) of the labeled amount of ondansetron is dissolved.
Test 5:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.
Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis:  Proceed as directed for Test 1.
Time:  30 min
Tolerances:  NLT 70% (Q) of the labeled amount of ondansetron is dissolved.
Test 6:  If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.
Medium:  Water; 500 mL, deaerated
Apparatus 2:  50 rpm
Time:  30 min
Buffer:  3.12 g/L of monobasic sodium phosphate dihydrate. Adjust with 1 N sodium hydroxide to a pH of 5.4.
Mobile phase:  Acetonitrile and Buffer (40:60)
Standard solution 
For Tablets labeled to contain 4 or 24 mg:  0.01 mg/mL of USP Ondansetron Hydrochloride RS in Medium
For Tablets labeled to contain 8 mg:  0.02 mg/mL of USP Ondansetron Hydrochloride RS in Medium
Sample solution 
For Tablets labeled to contain 4 or 8 mg:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
For Tablets labeled to contain 24 mg:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Further dilute 4.0 mL of this solution with Medium to 25.0 mL.
Chromatographic system 
Mode:  LC
Detector:  UV 216 nm
Column:  4.6-mm × 5-cm; 5-µm packing L10
Flow rate:  2.0 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of ondansetron (C18H19N3O) dissolved:
Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × V × D × 100
rU== peak response of the Sample solution
rS== peak response of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== label claim (mg/Tablet)
Mr1== molecular weight of ondansetron, 293.36
Mr2== molecular weight of ondansetron hydrochloride (anhydrous), 329.83
V== volume of Medium, 500 mL
D== dilution factor of the Sample solution
Tolerances:  NLT 75% (Q) of the labeled amount of ondansetron is dissolved.(RB 1-Jul-2011)
•  Uniformity of Dosage Units 905: Meet the requirements
IMPURITIES
•  Organic Impurities
Buffer and Mobile phase:  Proceed as directed in the Assay.
System suitability solution:  0.05 and 0.1 mg/mL of USP Ondansetron Related Compound A RS and USP Ondansetron Hydrochloride RS, respectively, in Mobile phase
Standard stock solution:  Use the Standard solution in the Assay.
Standard solution:  1.5 µg/mL of ondansetron in Mobile phase from the Standard stock solution
Sample solution:  Weigh and crush NLT 20 Tablets. Transfer a quantity of powder, equivalent to 50 mg of ondansetron, to a 100-mL volumetric flask. Add about 70 mL of Mobile phase, and sonicate for about 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Pass a portion of the solution through a suitable nylon filter of 0.45-µm pore size, and use the filtrate.
Chromatographic system:  Proceed as directed in the Assay.
Run time:  At least 45 min for the Sample solution
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
Resolution:  NLT 2.0 between ondansetron related compound A and ondansetron, System suitability solution
Relative standard deviation:  NMT 5.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak response of each individual impurity from the Sample solution
rS== peak response of ondansetron from the Standard solution
CS== concentration of ondansetron (free base) in the Standard solution (mg/mL)
CU== nominal concentration of ondansetron in the Sample solution (mg/mL)
F== relative response factor (see Table 1)
Acceptance criteria:  See Table 1.
Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
2-Methyl imidazolea 0.22 0.53 0.2
Ondansetron related compound Cb 0.40 1.2 0.2
Ondansetron related compound Dc 0.47 1.3 0.1
Ondansetron related compound Ad 0.87 0.90 0.2
Desmethylondansetrona,e 0.90 0.91 0.2
Ondansetron 1.0
Any other individual, unspecified degradation product 1.0 0.2
Total impurities 1.0
a  Not to be included in total impurities.
b  1,2,3,9-Tetrahydro-9-methyl-4H-carbazol-4-one.
c  1,2,3,9-Tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one.
d  3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.
e  1,2,3,9-Tetrahydro-9-methyl-3-[1H-imidazol-1-yl)methyl]-4H-carbazol-4-one.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.
•  Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
•  USP Reference Standards 11
USP Ondansetron Hydrochloride RS Click to View Structure
USP Ondansetron Related Compound A RS
3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.
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